Ewa Gorczyńska

Publications of Ewa Gorczyńska

• Matched Sibling Versus Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Acquired Aplastic Anemia: Experience of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

  Authors: Dawid Szpecht, Ewa Gorczyńska, Krzysztof Kałwak, Joanna Owoc-Lempach, Marta Choma, Jan Styczyński, Jolanta Goździk, Agnieszka Dłużniewska, Mariusz Wysocki, Jerzy R Kowalczyk, Alicja Chybicka, Anna Pieczonka, Jacek Wachowiak

  Archivum immunologiae et therapiae experimentalis. 04/2012;

  In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelatedIn the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

• [Assessment of lipid layer thickness of tear film in the diagnosis of dry-eye syndrome in children after the hematopoietic stem cell transplantation].

  Authors: Małgorzata Kurpińska, Ewa Gorczyńska, Joanna Owoc-Lempach, Aleksandra Bernacka, Marta Misiuk-Hojło, Alicja Chybicka

  Klinika oczna. 01/2011; 113(4-6):136-40.

  Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is recognized as the most frequent ocular complication after allogeneic stem cell transplantation (allo-SCT). KCS can appearDry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is recognized as the most frequent ocular complication after allogeneic stem cell transplantation (allo-SCT). KCS can appear either due to insufficient tear production or excessive tear evaporation, both resulting in tears hyperosmolarity that leads to ocular damage. The evaporation rate and better film stability is determined primarily by the status of the lipid layer. Observation and classification of tear film lipid layer interference patterns in normal and dry eyes in patients after allogeneic stem cell transplantation with a follow-up time of 6 months-5 years (median 26.54 months). Investigation of the relation between the lipid layer interference patterns in normal and dry eyes and the results of other dry eye examinations and complaints. Relation between DES and conditioning regimes, including total body irradiation and high-dose chemotherapy, immunosuppressive drugs, the time after allogeneic stem cell transplantation and chronic graft-versus-host disease. Precorneal tears lipid layer interference patterns, were examined in 114 eyes in treatment group with the Tearscope-plus. Patient with dry eye were identified on the basis of Schirmer test scores and/or tear breakup time, and positive lissamine and/or fluorescein staining. 42 of 114 eyes (36.8%) developed DES after allo-SCT A significant correlation between thickness of lipid layer and BUT, Schirmer test, lissamine green and fluorescein staining was found in the treatment group. A significant association was found between present chronic GVHD and DES in children. DES was not associated with TBI, corticosteroids, immunosuppressive drugs and the time in the present study. Tears lipid layer interference patterns are highly correlated with the diagnosis of DES. Tears lipid layer interference patterns ( noninvasive method), can be used to diagnose early DES in children after allo-SCT. Chronic GVHD play a major role in development of DES. dry eye syndrome, graft versus host disease, stem cell transplantation.

• PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients.

  Authors: Iwona Bil-Lula, Marek Ussowicz, Blanka Rybka, Danuta Wendycz-Domalewska, Renata Ryczan, Ewa Gorczyńska, Krzysztof Kałwak, Mieczysław Woźniak

  Archives of virology. 12/2010; 155(12):2007-15.

  After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children,After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations.

• Higher CD34(+) and CD3(+) cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell transplantation in children.

  Authors: Krzysztof Kałwak, Julita Porwolik, Monika Mielcarek, Ewa Gorczyńska, Joanna Owoc-Lempach, Marek Ussowicz, Agnieszka Dyla, Jakub Musiał, Dominika Paździor, Dominik Turkiewicz, Alicja Chybicka

  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 04/2010; 16(10):1388-401.

  The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+)The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.

• Treosulfan-based conditioning regimen in a second matched unrelated peripheral blood stem cell transplantation for a pediatric patient with CGD and invasive aspergillosis, who experienced initial graft failure after RIC.

  Authors: Maja Klaudel-Dreszler, Krzysztof Kalwak, Magdalena Kurenko-Deptuch, Beata Wolska-Kusnierz, Edyta Heropolitanska-Pliszka, Barbara Pietrucha, Bożena Mikoluc, Ewa Gorczyńska, Marek Ussowicz, Alicja Chybicka, Ewa Bernatowska

  International journal of hematology. 10/2009;

  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. InvasiveChronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. Invasive aspergillosis (IA) is the leading cause of mortality in patients with CGD. We report the case of a 3-year-old boy with CGD, who developed IA despite antifungal prophylaxis. His treatment consisted of a 10-month-long multi-drug antifungal therapy, together with surgery, but these did not cause any substantial clinical improvement. BMT in high-risk patients with CGD remains a challenge due to both, higher risk of graft rejection and inflammatory flare in the course of immune recovery. Our patient rejected the first matched unrelated donor (MUD) allograft after RIC regimen recommended by the EBMT Inborn Errors Working Party for high-risk patients. After treosulfan-based conditioning and second MUD peripheral blood stem cell transplantation both, full reconstitution of the granulocytic series and complete recovery from IA, were achieved.

• [Autologous stem-cell transplantations in children with non-Hodgkin lymphomas]

  Authors: Beata Wójcik, Jerzy R Kowalczyk, Alicja Chybicka, Jacek Wachowiak, Katarzyna Drabko, Agnieszka Zaucha-Prazmo, Marta Choma, Ewa Gorczyńska, Jacek Toporski, Dominik Turkiewicz, Krzysztof Kałwak, Anna Pieczonka, Dariusz Boruczkowski

  Przegla̧d lekarski. 02/2004; 61 Suppl 2:53-6.

  From January 1st 1995 to March 31st 2003 a total of 51 autologous stem-cell transplantations (auto-HSCT) in 49 children with non Hodgkin lymphomas (NHL) were carried out in the transplantationFrom January 1st 1995 to March 31st 2003 a total of 51 autologous stem-cell transplantations (auto-HSCT) in 49 children with non Hodgkin lymphomas (NHL) were carried out in the transplantation centres of the Polish Pediatric Group for Treating Leukemias and Lymphomas (PPGLBC). In 2 patients the transplantations were carried out twice. The age of children at the moment of the transplantation ranged from 2.8 to 17.3 years (median 10.0), with higher representation of boys than girls. Twenty eight of the procedures were carried out in children with the diagnosis of B-cell non Hodgkins lymphoma (B-NHL), eight--in children with non B-cell non Hodgkins lymphoma (NB-NHL) and thirteen--in patients with anaplastic large cell lymphoma (LCAL). 16 procedures were performed in children who at the moment of transplantation were in their first complete remission (CR), another 16 were carried out while in their 2nd and 3rd CRs, and 17 transplants were performed at partial remission (PR). In addition, two children received transplants in the phase of the disease relapse. In most cases (44) the BEAM protocol was applied as megachemotherapy. In 49 procedures peripheral blood was the source of stem-cells, in one--bone marrow, in one--bone marrow + peripheral blood. The number of CD34/kg cells transplanted ranged from 1.2 x 10(6) to 8.0 x 10(6) (median 4.2 x 10(6)). Hematologic reconstitution occurred in all but one patient who died on the 10th day from HSCT. 42 out of the 49 children (87%) survived with the observation time ranging from 1 to 94 months (median 47 months). During the observation time, 34 of children were in CR. In 15, disease relapses or progression were noted within the time ranging from 3 to 22 months from HSCT (median 6 months). Seven children died (14%) including 5 due to relapse. Expected overall survival (OS) at 5 years from transplantation for the whole group of patients was 0.85 and varied only slightly for individual categories of NHL. The probability of 5-year disease-free survival (DFS) for the whole group was 0.67 and was the highest in B-NHL (0.84) and was much lower in LCAL and in NB-NHL, 0.5 and 0.47 respectively. Our results suggest that BEAM megachemotherapy with autologous transplantation in children with NHL is a safe procedure, which at the same time improves the results of standard treatment, especially in children with NHL primary resistant to chemotherapy.

• Immunologic effects of intermediate-dose IL-2 i.v. after autologous hematopoietic cell transplantation in pediatric solid tumors.

  Authors: Krzysztof Kalwak, Marek Ussowicz, Ewa Gorczyńska, Dominik Turkiewicz, Jacek Toporski, Grzegorz Dobaczewski, Elzbieta Latos-Grazyńska, Renata Ryczan, Dorota Noworolska-Sauren, Alicja Chybicka

  Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 05/2003; 23(4):173-81.

  Adoptive immunotherapy with interleukin-2 (IL-2) may control minimal residual disease (MRD) and prevent relapse after autologous hematopoietic cell transplantation (AHCT). The objective of this studyAdoptive immunotherapy with interleukin-2 (IL-2) may control minimal residual disease (MRD) and prevent relapse after autologous hematopoietic cell transplantation (AHCT). The objective of this study was to determine the immunologic effects of intermediate doses of intravenous (i.v.) IL-2 after AHCT in children with poor-prognosis solid tumors. Eleven patients received a median five cycles consisting of escalating doses of IL-2 i.v. for 5 days after a median time interval of 94 days post-AHCT. The phenotype of lymphocyte subsets was investigated before and after each cycle, and parallel determination of natural killer (NK) cell activity was performed. Immunotherapy induced a significant increase in total lymphocyte count (TLC), T, NK, and, to some extent, B cells. Among NK cells, CD56+ bright cells expanded more than CD56+ dim cells. High expansion of CD56+ cells with CD94 inhibitory receptor was observed, whereas no difference was recorded in the number of CD3+ CD56+ and CD8+ CD57+ cells. NK activity stabilized after the first cycle of IL-2 and remained elevated during the study period. Cycles of IL-2 immunotherapy induced repeated significant expansion of T cells and NK cells, mostly of the immature CD56+ bright phenotype. Despite enhanced NK activity, relapses occurred frequently, which might have been due to increased CD94 activation and a poor response from the cytotoxic NK T cells and CD8+ CD57+ T cells.

• Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery.

  Authors: Krzysztof Kalwak, Ewa Gorczyńska, Jacek Toporski, Dominik Turkiewicz, Malgorzata Slociak, Marek Ussowicz, Elzbieta Latos-Grazyńska, Marzena Król, Janina Boguslawska-Jaworska, Alicja Chybicka

  British journal of haematology. 07/2002; 118(1):74-89.

  Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. WeImmune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, type of HCT, diagnosis, graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection reactivation. Absolute counts of different lymphocyte subsets and immunoglobulin serum levels were determined in peripheral blood of patients on d -7 and +16, and then at various intervals up to 24 months post transplant. Common patterns of immune recovery after both allogeneic and autologous HCT were identified: (i) CD4+CD45RO+ peripheral T-cell expansion on d +16; (ii) inverted CD4+:CD8+ ratio from d +30 onwards; (iii) rapid natural killer (NK) cell (CD16+/-CD56+) count normalization. We observed prolonged T-cell lymphopenia (CD3+, CD3+CD4+, CD4+CD45RA+) until 24 months after autologous HCT, whereas in the allogeneic setting CD3+CD4+ cells, including naive CD45RA+ cells, returned to normal values at 9 months post transplant. Age > 10 years and coexistence of GvHD and CMV reactivation were associated with a substantial delay in T- (CD4+, including CD45RA+) and B-cell recovery after allogeneic HCT. Multidrug GvHD prophylaxis resulted in impaired T- (CD4+, CD4+CD45RA+) and B-cell reconstitution only in the early phase after allogeneic HCT (up to 4 months). Our results demonstrated that T-cell recovery was severely impaired in children after autologous HCT. It should be emphasized that specific approaches to enhance immune reconstitution are necessary to control minimal residual disease and avoid the risk of infectious complications in the autologous setting. Thymic involution after allogeneic HCT seems to be associated with age and coexistence of GvHD and CMV reactivation.

• [High-dose therapy followed by auto HSCT in children--with advanced neuroblastoma in four transplant centres in Poland]

  Authors: Agnieszka Zaucha-Prazmo, Katarzyna Drabko, Beata Wójcik, Marta Choma, Krzysztof Kałwak, Ewa Gorczyńska, Dominik Turkiewicz, Małgorzata Słociak, Marek Ussowicz, Agnieszka Dyla, Alicja Chybicka, Jolanta Goździk, Mariusz Ratajczak, Jan Styczyński, Robert Debski, Mariusz Wysocki, Jerzy Kowalczyk

  Medycyna wieku rozwojowego. 10(3 Pt 1):775-84.

  AIM OF THE STUDY: Posttransplant morbidity and clinical outcome in children with advanced neuroblastoma (NBL) who underwent megachemotherapy followed by HSCT were investigated. PATIENTS AND METHODS:AIM OF THE STUDY: Posttransplant morbidity and clinical outcome in children with advanced neuroblastoma (NBL) who underwent megachemotherapy followed by HSCT were investigated. PATIENTS AND METHODS: In the study 73 children with advanced NBL treated in four Departments of Paediatric Haematology and Oncology in Lublin, Kraków, Wrocław and Bydgoszcz from 1995 to 2004 were analysed. Median age of children was 4.9 years (range 1.8 to 15). Reinfusion of CD34 cells followed myeloablative chemotherapy with Busulfan / Melfalan in 58 patients; Treosulfan / Melfalan in 2 patients; Melfalan / VP16/ Carbo in 9 patient, Melfalan alone in 3 patients and Thiotepa /CTX/ Carbo in 1 patient. Stem cells from peripheral blood were used in 57 cases, bone marrow in 10 patients, bone marrow and peripheral blood in 6 patients. RESULTS: 41/73 (56%) children are alive with median follow up 12 months (range 3 to 68 months), 29 children are in complete remission (CR), 12 patients are in partial remission (PR). 32/73 (44%) children died, 26 of them due to progressive disease; six children died due to posttransplantation complications. Overall survival (OS) at median observation time 12 months is 0.65; disease free survival (DFS) is 0.58. Probability of 5-year OS and DFS in the group of children transplanted in first partial/complete remission are 0.42 and 0.4 respectively. CONCLUSIONS: Treatment with megachemotherapy followed by autoHSCT in patients with advanced neuroblastoma has not many adverse effects. Probabilities of 5-year OS and DFS are higher in the group of transplanted children in 1 partial/complete remission than in children transplanted after relapse.

• [Megachemotherapy and autologous hematopoietic stem cell transplantation in children with solid tumours excluding neuroblastoma--experience of Polish paediatric centres]

  Authors: Katarzyna Drabko, Marta Choma, Agnieszka Zaucha-Prazmo, Beata Wójcik, Ewa Gorczyńska, Krzysztof Kałwak, Dominik Turkiewicz, Małgorzata Słociak, Marek Ussowicz, Agnieszka Dyla, Alicja Chybicka, Jan Styczyński, Robert Debski, Mariusz Wysocki, Jolanta Goździk, Mariusz Ratajczak, Jerzy R Kowalczyk

  Medycyna wieku rozwojowego. 10(3 Pt 1):785-92.

  AIM OF THE STUDY was to present the experience of four Polish transplantation centres (Wroclaw, Bydgoszcz, Kraków and Lublin) with use of megachemotherapy (MCT) and autologous hematopoietic stem cellAIM OF THE STUDY was to present the experience of four Polish transplantation centres (Wroclaw, Bydgoszcz, Kraków and Lublin) with use of megachemotherapy (MCT) and autologous hematopoietic stem cell transplantation (autoHSCT) in children with high risk solid tumours. PATIENTS AND METHODS: Between 1994 and 2005 in 67 patients, whose age ranged form 1.5 to 20 years, 74 procedures of megachemotherapy and auto HSCT were performed. 25 children were treated for Ewing Sarcoma, 13 for rhabdomyosarcoma embryonale (RMS), 7 for germinal tumours, 6 for medulloblastoma, 4 for PNET, 4 for Wilm's tumours, 2 for glioblastoma and single patients with mesenchymoma, astrocytoma, ependymoma, angioblastoma, carcinoma ovarian and carcinoma embryonale glutei. Most common megachemotherapy protocols consisted of: Melphalan, Etopozyd i Carboplatin (MEC)--applied in 24 children and Busulfan plus Melphalan (Bu Mel) administered in 19 patients. In 29 children MCH was introduced in first complete remission, in 14 the procedure was performed in second or subsequent remission and 24 patients did not achieve remission before megachemotherapy was started. RESULTS: 30 children are alive (44%), 28 of them in complete remission of disease. 23 out of 29 (79%) patients were transplanted in first complete remission and median observation time in that group is 29 months (range 2-74 months). Only 5 out of 38 children transplanted in second complete remission or without complete remission survived. 39 patients relapsed at a median time 11 months after MCT and 37 of them subsequently died of disease at a median time of 16 months. One toxic death was noted--it was a boy, transplanted with progressive disease. CONCLUSIONS: 1. Megachemotherapy with autologous stem cell can rescue children with high risk solid tumours. It is a safe procedure especially when performed in remission. 2. Children with resistant or relapsed solid tumours are unlikely to benefit from megachemotherapy.